Improving pancreatic islet in vitro functionality and transplantation efficiency by using heparin mimetic peptide nanofiber gels

Abstract

Pancreatic islet transplantation is a promising treatment for type 1 diabetes. However, viability and functionality of the islets after transplantation are limited due to loss of integrity and destruction of blood vessel networks. Thus, it is important to provide a proper mechanically and biologically supportive environment for enhancing both in vitro islet culture and transplantation efficiency. Here, we demonstrate that heparin mimetic peptide amphiphile (HM-PA) nanofibrous network is a promising platform for these purposes. The islets cultured with peptide nanofiber gel containing growth factors exhibited a similar glucose stimulation index as that of the freshly isolated islets even after 7 days. After transplantation of islets to STZ-induced diabetic rats, 28 day-long monitoring displayed that islets that were transplanted in HM-PA nanofiber gels maintained better blood glucose levels at normal levels compared to the only islet transplantation group. In addition, intraperitoneal glucose tolerance test revealed that animals that were transplanted with islets within peptide gels showed a similar pattern with the healthy control group. Histological assessment showed that islets transplanted within peptide nanofiber gels demonstrated better islet integrity due to increased blood vessel density. This work demonstrates that using the HM-PA nanofiber gel platform enhances the islets function and islet transplantation efficiency both in vitro and in vivo.

Angiogenic peptide nanofibers repair cardiac tissue defect after myocardial infarction

“…It is important to stress that in addition to increasing only the volume of an area similarly to other injectable gels, angiogenic bioactivity of GAG mimetic nanofiber hydrogels is critical in inducing angiogenesis, which ensures a steady supply of oxygen and nutrients to the ischemic area. These peptide nanofibers were recently used to transplant pancreatic islets and shown to improve both viabilities of islets and number of intraomental vessels in diabetic rats [39]. Similarly, in this work, we observed improved cardiomyocyte protection with reduced degree of fibrosis and a significant increase in mature blood vessel formation.…”

Nanomaterials as potential and versatile platform for next generation tissue engineering applications

“…Through pancreas TE, development of a bioengineered pancreas has been achieved by appropriate combination of cells, biomaterial scaffolds, and biologically active molecules that could help in islet regeneration and transplantation as an alternative avenue for diabetes therapy . Islet transplantation also has certain limitations like lack of islet donors, difficulty in isolation of islets, decrease in viability during isolation, and damage of intra‐islet vasculature . In the initial days of transplantation, alternative transplantation sites and supportive scaffolds were used in order to minimize the immunological responses and also to increase the islet viability, but still the viability issues exist.…”

“…82,83 Islet transplantation also has certain limitations like lack of islet donors, difficulty in isolation of islets, decrease in viability during isolation, and damage of intra-islet vasculature. 84 In the initial days of transplantation, alternative transplantation sites and supportive scaffolds were used in order to minimize the immunological responses and also to increase the islet viability, but still the viability issues exist. In the recent era, nanotechnological approaches were implanted to design NMs for repair and regeneration of pancreatic islets.…”

Tissue‐engineered islet‐like cell clusters generated from adipose tissue‐derived stem cells on three‐dimensional electrospun scaffolds can reverse diabetes in an experimental rat model and the role of porosity of scaffolds on cluster differentiation

“…In addition, it allows fast revascularization of grafted islets and prevents early islet loss (Berman et al, 2009), and protects the islets from high blood pressure as experienced in portal vein transplantation model (Uzunalli et al, 2015). The ability of differentiated ILCs on large lattice scaffolds to reverse hyperglycemia in diabetic rats as compared to the rat mature islets seeded in large lattice scaffolds.…”